1. Field of the Invention
This invention relates to mobile applications. Specifically, the invention relates to mobile applications for hemolysis detection.
2. Brief Description of the Prior Art
Prenatal conditions are the fourth leading cause of death in developing nations and still pose significant health risks in countries with high income. Preeclampsia is a prenatal complication associated with high blood pressure and organ failure, which can result in potential maternal and/or fetal compromise and/or loss (Roberts, J. M. “Endothelial dysfunction in preeclampsia. Seminars in reproductive endocrinology”. 1998. GEORG THIEME VERLAG; Habli, M. and B. Sibai. “Hypertensive disorders of pregnancy”. Danforth's Obstetrics and Gynecology, 2008: p. 257-275). Globally, preeclampsia and other hypertensive disorders of pregnancy are a leading cause of maternal and infant illness and death. Its complications are the reason for 25% of maternal deaths worldwide in addition to fetal and neonatal death. By conservative estimates, these disorders are responsible for 76,000 maternal and 500,000 infant deaths each year. Preeclampsia can rapidly escalate to a dangerous complication known as HELLP syndrome. What is needed is a mechanism of detecting the first signs of this deadly complication while the mother is still stable and the baby can be promptly delivered, since this is the only opportunity to save their lives.
According to the Preeclampsia Foundation, the mortality rate of HELLP syndrome has been reported to be as high as 25%. HELLP syndrome can be difficult to diagnose, especially when high blood pressure and protein in the urine are not present. Its symptoms are sometimes mistaken for gastritis, flu, acute hepatitis, gall bladder disease, or other conditions. Among pregnant women in the United States, about 5% to 8% develop preeclampsia. It is estimated that about 15% of those women will develop evidence of HELLP syndrome. This mean as many as 48,000 women per year will develop HELLP syndrome in the U.S.
Most often, the definitive treatment for women with HELLP Syndrome is the delivery of their baby. During pregnancy, many women suffering from HELLP syndrome require a transfusion of some form of blood product (red cells, platelets, plasma). Corticosteroids can be used in early pregnancy to help the baby's lungs mature. Some healthcare providers may also use certain steroids to improve the mother's outcome, as well.
Overall, perinatal mortality from HELLP Syndrome (stillbirth plus neonatal death) ranges from about 7.7% to 60%. Most of these deaths are attributed to abruption of the placenta (placenta prematurely separating from the uterus), placental failure with intrauterine asphyxia (fetus not getting enough oxygen), and extreme prematurity.
The most reliable method of treatment is expedited delivery of the baby. Early diagnosis of this complication is difficult as most of its symptoms are non-specific. Current testing technologies require sending blood samples to the lab when early HELLP syndrome is suspected. By the time results of the test are available, the condition of the patient has already severely deteriorated.
One of the key signs of HELLP syndrome is the occurrence of in vivo hemolysis—a condition which occurs when red blood cells (RBCs) are lysed releasing hemoglobin into blood plasma. Free plasma hemoglobin in healthy individuals is 0.001-0.004 g/dL (Giuseppe Lippi, G. C., Emmanuel J. Favaloro, Mario Plebani, “Hemolysis, An Unresolved Dispute in Laboratory Medicine”, In Vitro and In Vivo Hemolysis 2012). When it reaches a level of 0.01 g/dL, it indicates hemolysis, and during severe hemolytic episodes it can exceed 1 g/dL. (Rother, R. P., et al., “The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: A novel mechanism of human disease”, JAMA, 2005. 293(13): p. 1653-1662. Rosse, W. F., “Paroxysmal nocturnal hemoglobinuria-present status and future prospects”, West J Med, 1980. 132(3): p. 219-28). The increase of hemoglobin concentration in blood above 0.01 g/dL is extremely dangerous, and by the time it reaches 0.1 g/dL the condition of the patient deteriorates so significantly that HELLP syndrome becomes obvious and immediate reaction is needed for saving the patient's life. Presence of high concentration of hemoglobin in plasma results in multiple organ failure and potentially death.
Blood testing is the most frequently performed medical procedure, and the number of blood tests in the US is measured in hundreds of millions per year. Several percent of those tests have to be repeated because of in vitro hemolysis—disruption of the red blood cells and release of hemoglobin and other intercellular content into plasma. Hemolysis is generally detected via visual assessment of plasma, but this is very inaccurate (see FIG. 7, where hemolyzed samples are analyzed visually). Hemolysis cannot be detected in whole blood because of the presence of cells; therefore, centrifugation and plasma separation are required to assess level of hemoglobin in plasma. This can introduce critical delays that can potentially result in death. Additionally, in resource-poor environments, sample pre-processing might be impossible because of a lack of access to hematology labs and trained specialists. Still, prompt detection of hemolysis near patient is critical for saving the lives of the mother and the fetus; however, the current technologies do not support such functionality.
Increase in concentration of hemoglobin in plasma results in color change from clear or yellow to red, when the sample is grossly hemolyzed. The visual assessment is very unreliable, does not provide any quantitative information, and may be even more complicated by elevated concentration of other blood components, such as bilirubin. While there are hemoglobin colorimetric assays allowing measurement of hemoglobin concentration from 0.005 g/dL to 0.5 g/dL, they all require sample preprocessing introducing critical delays to hemolysis detection. Current methods of detecting hemolysis only work with blood plasma, require extensive time for sample preprocessing, and must use large instruments on large blood samples (i.e., milliliters of blood), thus making them inapplicable to near patient analysis.
Accordingly, what is needed is a device and methodology that can utilize just a drop of whole blood and be able to promptly and reliably measure hemoglobin concentration in plasma. However, in view of the art considered as a whole at the time the present invention was made, it was not obvious to those of ordinary skill in the field of this invention how the shortcomings of the prior art could be overcome.
All referenced publications are incorporated herein by reference in their entirety. Furthermore, where a definition or use of a term in a reference, which is incorporated by reference herein, is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
While certain aspects of conventional technologies have been discussed to facilitate disclosure of the invention, Applicants in no way disclaim these technical aspects, and it is contemplated that the claimed invention may encompass one or more of the conventional technical aspects discussed herein.
The present invention may address one or more of the problems and deficiencies of the prior art discussed above. However, it is contemplated that the invention may prove useful in addressing other problems and deficiencies in a number of technical areas. Therefore, the claimed invention should not necessarily be construed as limited to addressing any of the particular problems or deficiencies discussed herein.
In this specification, where a document, act or item of knowledge is referred to or discussed, this reference or discussion is not an admission that the document, act or item of knowledge or any combination thereof was at the priority date, publicly available, known to the public, part of common general knowledge, or otherwise constitutes prior art under the applicable statutory provisions; or is known to be relevant to an attempt to solve any problem with which this specification is concerned.